口服小分子氨酸激酶2和固酶4抑制剂在斑块性牛皮症:一个网络的元分析
Yuanyuan Xu1,2, Zhixuan Li1,2, Shuwei Wu1,2
1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China.
Frontiers in immunology
|June 19, 2023
概括
新的口服小分子药物,包括氨酸激酶2 (TYK2) 和固酶4 (PDE4) 抑制剂,对斑块性牛皮具有前途. 德乌克拉维西丁尼和罗普萨西丁尼显示出优越的疗效和与阿普雷米拉斯特相比的安全性.
科学领域:
- 药理学和皮肤病学
- 针对免疫媒介疾病的全身疗法.
背景情况:
- 斑块性牛皮是一种慢性炎症状况,可以通过全身疗法治疗.
- 口服小分子药物,如氨酸激酶2 (TYK2) 和固酶4 (PDE4) 抑制剂,代表了新的治疗选择.
- 对这些新兴的口服药物在牛皮的疗效和安全性数据的比较是有限的.
研究的目的:
- 进行网络元分析,比较口服TYK2和PDE4抑制剂对中度至重度斑块性牛皮的疗效和安全性.
- 评估这些新型口服药物的应答率 (PASI-75,PGA 0/1) 和不良事件 (AEs),与安慰剂和现有治疗方法 (如阿普雷米拉斯特) 相比.
主要方法:
- 在PubMed,Embase和Cochrane图书馆对随机临床试验 (RCT) 的系统文献搜索.
- 贝叶斯的多重治疗网络元分析 (NMA) 来合成疗效 (PASI-75,PGA 0/1) 和安全性 (AE发病率) 数据.
- 包括13个RCT与5274名患者评估TYK2和PDE4抑制剂.
主要成果:
- 德乌克拉维西替尼 (不同剂量),罗普萨西替尼 (200,400毫克QD) 和阿普雷米拉斯 (20,30毫克两次) 的PASI和PGA反应率高于安慰剂.
- 德乌克拉维西提尼布和罗普萨西提尼布 (特定剂量) 与阿普雷米拉斯特 (每天两次30毫克) 相比,表现出更高的疗效.
- 与阿普雷米拉斯特 (每日两次30毫克) 相比,没有观察到德乌克拉维西替尼或罗普西替尼对不良事件的显著增加.
结论:
- 口服TYK2抑制剂,特别是deucravacitinib,在治疗斑块性牛皮方面表现出显著的疗效,在某些剂量下表现优于apremilast.
- 这些发现支持口服TYK2抑制剂作为斑块性牛皮的有效系统疗法的潜力.
- 需要进一步进行大规模的长期研究,以充分阐明新型TYK2抑制剂的特征.
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